Serum lipase levels pre and post Landh meal: Evaluation of exocrine pancreatic status in cystic fibrosis

Determination of pancreatic function is essential in cystic fibrosis. The most-reliable method is by measuring pancreatic enzymes in the duodenum following intravenous or oral stimulation. However, this is invasive, time consuming, and expensive. Indirect tests are non-invasive but lack accuracy. This study examines a simple test which combines pancreatic stimulation by Lundh meal and sequential serum lipase measurements. The test was performed on three groups: group A, 36 cystic fibrosis patients carrying two mutations associated with severe disease and pancreatic insufficiency (ΔF508, W1282X, G542X, N1303K, S549R); group B, 8 compound heterozygote cystic fibrosis patients carrying one mutation causing mild disease with pancreatic sufficiency (3849 + 10 kb C → T); group C, 17 healthy individuals. Basal lipase levels were 2–16.5, 16.4–73, and 8.5–27.8 U/l in groups A, B, and C, respectively, with some overlapping between groups. There were three patterns of lipase activity (1) consistently low levels (group A) suggested a severely affected insufficient pancreas; (2) normal basal levels followed by a linear rise peaking 30 min after the meal (found in 16 of 17 healthy individuals and 3 patients of group B) reflecting an unaffected sufficient pancreas; (3) elevated lipase levels not influenced by the meal (5 patients of group B). This reflects an ongoing destructive process in the pancreas which will eventually result in conversion from pancreatic sufficiency to pancreatic insufficiency. Hence serum lipase activity prior to and 30 min after Lundh meal is a good indicator of pancreatic status allowing categorization of cystic fibrosis patients as pancreatic insufficient, pancreatic sufficient, or pancreatic sufficient with late conversion to insufficiency.     

Comparative study of secretin and Lundh tests.

Exocrine pancreatic function in 19 patients with pancreatic disease and in 14 of 16 controls was measured by secretin stimulation and by the Lundh test on two different occasions. Peak bicarbonate concentration in the Lundh test emerged as the most reliable parameters. No additional diagnostic value was obtained by measuring enzymes after secretin injection. In 6 patients with chronic and in 8 of 13 patients with acute pancreatitis, both tests gave results that agreed with each other. The remaining 5 patients showed either an abnormal secretin value or an abnormal Lundh test. This is consistent with the wide variation seen in acute pancreatitis. It is concluded that the Lundh test as well as the secretin test were of value in the assessment of chronic pancreatic disease. The secretin test may be slightly more sensitive to mild and acute pancreatic damage than is the Lundh test. However stimulation of the pancreas by a test meal is easier to perform and more economic.     

Lundh meal: a single non-invasive challenge test for evaluation of exocrine and endocrine pancreatic function in cystic fibrosis patients

The determination of endocrine and exocrine pancreatic function in cystic fibrosis patients is clinically important. Recently, a new non-invasive test, in which pancreatic stimulation by a Lundh meal is followed by sequential serum lipase measurements, was found to be a good indicator of exocrine pancreatic status. Since the Lundh meal also contains glucose, the present study assessed whether it also might be suitable for evaluation of the pancreatic endocrine axis. After an overnight fast, 10 healthy non-diabetic subjects and 14 cystic fibrosis patients ingested a Lundh meal. Glucose, insulin, and C peptide levels were measured at various time intervals following the meal. For purposes of comparison, the oral glucose tolerance test was also performed on the cystic fibrosis patients. All healthy subjects demonstrated an increase in glucose levels post Lundh meal, peaking at 45 min (mean 140+/-21 mg/dl) and then gradually declining and reaching the normal range at 120 min. Concordant peaks of insulin (46.3+/-20 IU/ml) and C peptide (5.8+/-1. 5 ng/ml) levels were noted at 60 min. All 14 cystic fibrosis patients had normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal oral glucose tolerance test, and their hemoglobin A(1C) levels were within the normal range. The other 6 cystic fibrosis patients demonstrated glucose levels above 200 mg/dl 30-60 min post Lundh meal, and all also had an impaired oral glucose tolerance test. Of these 6, 4 had high levels of hemoglobin A(1C). This study demonstrates that the Lundh meal challenges the endocrine pancreas as well as the oral glucose tolerance test. Thus, determination of both exocrine and endocrine pancreatic status can be achieved by a single non-invasive test.     

A Comparative Study of Four Tests of Pancreatic Function in the Diagnosis of Pancreatic Disease

Four tests of pancreatic function—the conventional andsubtraction pancreas scans, the Lundh test, and the radioseleniumtest—were performed in 80 patients in an attempt to clarifythe indications for performing one or more of these tests inthe diagnosis of pancreatic disease. All four tests were performedsimultaneously in a single two-hour session. The scans weremarked blindly by three independent observers. The radioselenium and Lundh tests were equally accurate in distinguishingbetween the normal and the abnormal pancreas. Thus only oneof these two tests need be performed in a patient referred forpancreatic investigation. Routine performance of both a conventional and a subtractionscan is, however, indicated because the subtraction scan gavefewer false positive results in normal patients whereas theconventional scan yielded better resolution of filling defects. A normal pancreatic scan indicated a 94 per cent probabilitythat the pancreas was normal. If the scan was normal the intubationtest was always normal. An abnormal intubation test indicateda 100 per cent probability that the pancreas was abnormal. Ifthe intubation test was abnormal the scan was always abnormal.However, abnormal (false positive) scans were seen in 25 percent of the normal subjects and normal (false negative) intubationtests were seen in 35 per cent of patients with pancreatic carcinoma.Abnormal scans were seen in 95 per cent of patients with pancreaticcarcinoma and in some instances the scans were very suggestiveof carcinoma as a localized filling defect was seen. Thus thepancreatic scan is more reliable than an intubation test inestablishing a diagnosis of pancreatic carcinoma. Diagnosticability can, in general, be best improved by performing eitherone of the duodenal intubation tests together with both theconventional and the subtraction scan. But for some patients,either the scans on their own (if normal) or an intubation testalone (if abnormal) will suffice. ¹This work formed part of an M.D. thesis submitted to CambridgeUniversity by G. R. Youngs.     

Diagnosis of chronic pancreatic disease.

The diagnosis of pancreatic disease is difficult. The first step is clinical suspicion, based on the symptoms and signs. If pancreatic disease is suspected, investigation is necessary to prove this diagnosis. Investigation aims to answer two questions: a) is there pancreatic disease and b) if so, what type? The first question may be answered by demonstrating abnormal pancreatic function, using pancreatic function tests, whereas the second is answered by using techniques to demonstrate structural (anatomical) abnormalities of the pancreas. a) The methods to establish abnormal pancreatic function consist of 1. tests to demonstrate abnormal digestive capability, 2. tests to study pancreatic exocrine secretion, and 3. tests to study endocrine secretion. The tests of group 1 are: chemical fat balance study before and during enzyme replacement therapy, faecal nitrogen balance study, and the demonstration of either the malabsorption of vitamins A, D and K or the sequelae of their malabsorption (low serum calcium, high alkaline phosphatase, prolonged prothrombin time, etc.). Abnormal vitamin B12 absorption also may be present. 2. The tests designed to study pancreatic exocrine secretion are determination of the presence or absence of proteolytic enzymes in the stool, the secretion test, the pancreozymin stimulation test and the Lundh test. The serum amylase and lipase values are of little help in assessment of pancreatic function. 3. The tests to study endocrine function are the glucose tolerances test (which frequently gives abnormal results in pancreatic disease), and radioimmunoassays for insulin and gastrointestinal hormones (which may be increased in patients with functioning tumours of the islet cells). b) The techniques used to establish structural abnormalities of the pancreas are: duodenal cytology (during secretin tests), radiological techniques (abdominal survey films, barium meal, hypotonic duodenography, roentgenography of the biliary tract, barium enema, and angiography,) gastroscopy, duodensocopy, endoscopy and retrograde pancreatography, echography, scan and laparotomy. The relative value of these tests is discussed.     

Fecal elastase-1 as a test for pancreatic function: a review.

Pancreatic elastase-1 is a specific human protease synthetized by the acinar cells. Immunoreactive elastase-1 cannot be detected in either porcine or bovine pancreatic enzyme preparations. It is very stable and, in contrast to fecal chymotrypsin, elastase is unaffected by exogenous pancreatic enzyme treatment, and correlates well with exocrine pancreatic function tests. The measurement of this proteolytic enzyme in stool by means of an enzyme-linked immunosorbent assay (ELISA) is a sensitive, specific, and relatively inexpensive non-invasive test. It is an accurate function test for patients with chronic pancreatitis confirmed by endoscopic retrograde cholangiopancreatography and computerized axial tomography. It shows higher sensitivity and specificity for exocrine pancreatic insufficiency than fecal chymotrypsin determination and is comparable to oral pancreatic function tests such as the pancreolauryl test.     

Preserved incretin effect after complete surgical denervation of the pancreas in young pigs

Plasma insulin responses to intragastric (i.g.) (1.5 g/kg b.wt.) and "isoglycemic" intravenous (i.v.) glucose were measured in ten unanesthetized young pigs to assess the contribution of gastrointestinal factors to the total insulin secretion as observed after i.g. glucose. The participation of nerves was estimated by comparing metabolic tests performed before and after total surgical pancreatic denervation. In the five animals which survived the procedure, 52.6% of the insulin response after i.g. glucose was calculated to be due to incretion factors, a value similar to the 54.8% found in the preoperative series (with intact pancreatic innervation). The response of IR-GIP to i.g. glucose was not significantly different between preoperative and postoperative tests, although a subtotal duodenectomy had to be performed in the course of the operation designed to completely denervate the pancreas. Intragastric and i.v. (also tested by bolus glucose injection) glucose tolerance was almost identical before and after the operation. It was concluded that nerves do not seem to play a major role in mediating the incretin effect in pigs. Hormonal factors, including GIP, appear to be more important.     

Update of exocrine functional diagnostics in chronic pancreatitis

Diagnostics of pancreatic insufficiency rely mainly on tests of pancreatic exocrine function based on either measurement of pancreatic secretion or the secondary effects resulting from lack of digestive enzymes or imaging modalities. These methods have been developing rapidly over the last decades, and the aims of this review were to describe exocrine functional testing and imaging of the pancreas in chronic pancreatitis..     

保留十二指肠的胰头切除术治疗胰头部占位性病变的临床研究

目的探讨保留十二指肠的胰头切除术在胰头部占位性病变治疗中的临床应用价值。方法回顾性分析2003～2009年间10例胰头部占位性病变患者接受保留十二指肠的胰头切除术的临床资料。结果术后平均住院时间为13 d,无手术死亡,无严重并发症发生。术后随访发现,保留十二指肠的胰头切除术的实施基本不影响患者术后胰腺内外分泌功能。结论保留十二指肠的胰头切除术是一种治疗胰头部占位性病变的理想术式。     

Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency

Abstract. There have been previous reports of evidence for increased insulin sensitivity in patients with intermittent claudication as the only symptom of arterial insufficiency. This study was designed to evaluate the role of peripheral tissue with respect to insulin sensitivity in such patients. Intravenous glucose tolerance tests (IVGTT) and intravenous insulin tolerance tests (IVITT) were performed in patients with peripheral arterial insufficiency and in controls. During IVGTT the plasma insulin values were significantly lower in patients with arterial insufficiency. During IVITT the venous concentration of glucose decreased more and the area over the glucose curve was significantly larger, suggesting a higher insulin sensitivity in this group. The low insulin values could not be referred to a larger distribution volume or an increased degradation rate, suggesting decreased pancreatic insulin release in this group. At the time of surgery for arterial insufficiency and for varicose veins in controls, the uptake of insulin and glucose and the release of lactate were measured over the leg before and after a glucose load. The uptake of insulin over the leg correlated positively with the arterial insulin concentration and the uptake of glucose in both groups. The insulin uptake had a tendency to be increased in legs with arterial insufficiency during the glucose challenge. The glucose uptake in the leg did not differ in the basal state, but was 3 times higher in the legs of patients with arterial insufficiency during glucose challenge. The increased glucose uptake in this group could be ascribed to a high insulin sensitivity in the leg, as defined by glucose uptake per unit of insulin taken up.     

Further evidence for the influence of intraduodenal pH on the PABA test

The effect of prior administration of 400 mg of cimetidine on the outcome of the PABA test was investigated. In 8 patients the PABA test result rose with on average 27.5% after the administration of cimetidine. Four of them were selected for these investigations, because a much lower PABA test result had been obtained than was expected from the Lundh test result. In one patient, the low PABA test result was in conflict with faecal fat excretion and the clinical condition. Three patients were selected with severe pancreatic dysfunction, as demonstrated by the PABA test, Lundh test and faecal fat excretion. The change effected by cimetidine was shown to be significantly related to duodenal pH and mean trypsin activity as measured in the Lundh test. In a control group of four patients with a PABA test result in the normal range, no significant effect of cimetidine administration was seen. The beneficial effect of cimetidine can be explained by its known inhibiting influence on gastric acid production, resulting in higher intraduodenal pH with subsequent enhanced enzymatic activity. The importance of intraduodenal pH for the PABA test result is further stressed by these results.     

Inflammatory myofibroblastic tumor of the pancreatic neck: A case report and review of literature

BACKGROUNDPancreatic inflammatory myofibroblastic tumor (IMT) is a relatively rare disease that is often confused with pancreatic cancer or pancreatic neuroendocrine tumors. The histological features of IMTs show that tissue from this type of tumor contains an intermingling of fibroblast and myofibroblast proliferation, accompanied by a varying degree of inflammatory cell infiltration.CASE SUMMARYThe management of an IMT occurring at the neck of the pancreas is presented in this paper. A 66-year-old female patient was diagnosed with a pancreatic neck mass after a series of tests. The patient underwent enucleation of the pancreatic neck tumor after a pathological diagnosis of IMT. Previous research on the clinical features, pathological diagnosis and treatment of pancreatic IMTs was reviewed. Compared with previous reports, this is a unique case of enucleation of a pancreatic IMT.CONCLUSIONThe enucleation of pancreatic IMTs may be a safe and efficient surgical method for managing such tumors with a better prognosis. Further cases are required to explore surgical measures for pancreatic IMTs.     

Chronic pancreatitis

Chronic pancreatitis is the progressive and permanent destruction of the pancreas resulting in exocrine and endocrine insufficiency and, often, chronic disabling pain. The etiology is multifactorial. Alcoholism plays a significant role in adults, whereas genetic and structural defects predominate in children. The average age at diagnosis is 35 to 55 years. Morbidity and mortality are secondary to chronic pain and complications (e.g., diabetes, pancreatic cancer). Contrast-enhanced computed tomography is the radiographic test of choice for diagnosis, with ductal calcifications being pathognomonic. Newer modalities, such as endoscopic ultrasonography and magnetic resonance cholangiopancreatography, provide diagnostic results similar to those of endoscopic retrograde cholangiopancreatography. Management begins with lifestyle modifications (e.g., cessation of alcohol and tobacco use) and dietary changes followed by analgesics and pancreatic enzyme supplementation. Before proceeding with endoscopic or surgical interventions, physicians and patients should weigh the risks and benefits of each procedure. Therapeutic endoscopy is indicated for symptomatic or complicated pseudocyst, biliary obstruction, and decompression of pancreatic duct. Surgical procedures include decompression for large duct disease (pancreatic duct dilatation of 7 mm or more) and resection for small duct disease. Lateral pancreaticojejunostomy is the most commonly performed surgery in patients with large duct disease. Pancreatoduodenectomy is indicated for the treatment of chronic pancreatitis with pancreatic head enlargement. Patients with chronic pancreatitis are at increased risk of pancreatic neoplasm; regular surveillance is sometimes advocated, but formal guidelines and evidence of clinical benefit are lacking.     

Surgical approaches to chronic pancreatitis: indications and imaging findings

Chronic pancreatitis (CP) is an irreversible, inflammatory process characterized by progressive fibrosis of the pancreas that can result in abdominal pain, exocrine insufficiency, and diabetes. Inadequate pain relief using medical and/or endoscopic therapies is an indication for surgery. The surgical management of CP is centered around three main operations including pancreaticoduodenectomy (PD), duodenum-preserving pancreatic head resection (DPPHR) and drainage procedures, and total pancreatectomy with islet autotransplantation (TPIAT). PD is the method of choice when there is a high suspicion for malignancy. Combined drainage and resection procedures are associated with pain relief, higher quality of life, and superior short-term and long-term survival in comparison with the PD. TPIAT is a reemerging treatment that may be promising in subjects with intractable pain and impaired quality of life. Imaging examinations have an extensive role in pre-operative and post-operative evaluation of CP patients. Pre-operative advanced imaging examinations including CT and MRI can detect hallmarks of CP such as calcifications, pancreatic duct dilatation, chronic pseudocysts, focal pancreatic enlargement, and biliary ductal dilatation. Post-operative findings may include periportal hepatic edema, pneumobilia, perivascular cuffing and mild pancreatic duct dilation. Imaging can also be useful in the detection of post-operative complications including obstructions, anastomotic leaks, and vascular lesions. Imaging helps identify unique post-operative findings associated with TPIAT and may aid in predicting viability and function of the transplanted islet cells. In this review, we explore surgical indications as well as pre-operative and post-operative imaging findings associated with surgical options that are typically performed for CP patients.     

Advances in the enzyme diagnosis of pancreatic diseases

This paper reviews recent developments of analytical methods for the determination of alpha-amylase, of its isoenzymes, and of lipase. The evaluation of severity and etiology of acute pancreatitis by enzyme assays, e.g., pancreatic elastase 1, phospholipase A2, and routine enzymes are discussed. The limited significance of enzyme determinations as compared to imaging and endoscopic procedures for the diagnosis of chronic pancreatitis is demonstrated. Indirect "tubeless" tests for the evaluation of pancreatic exocrine insufficiency with respect to the secretion of chymotrypsin (chymotrypsin in stool and NBT-PABA test) and cholesterol esterase (pancreolauryl test) are reviewed. Finally, the superiority of morphologic investigations over biochemical tests for the timely detection of pancreatic carcinoma is shown.     

Fecal chymotrypsin and elastase-1 determination on one single stool collected at random: diagnostic value for exocrine pancreatic status

OBJECTIVE: The secretin-cholecystokinin test is the "gold standard" to evaluate exocrine pancreatic function. But this direct duodenal intubation test is invasive, particularly in children, time-consuming, and expensive. For several years, indirect noninvasive tests of pancreatic insufficiency have been developed, such as fecal chymotrypsin (FChT) and fecal elastase-1 (FEL-1) measurements. Generally, elastase-1 is truly admitted to be the most relevant test of exocrine pancreatic status. However, so far, no consensus for stool collection protocol exists. The aim of our study was to investigate the diagnostic advantage from measuring fecal proteases in stool samples collected for two or three consecutive days in comparison to one single stool sample collected at random. DESIGN: A total of 69 children were divided into group A (stool samples collected for three consecutive days) and group B (stool samples collected for two consecutive days). These two groups included pancreatic-sufficient patients (PS) and severe pancreatic-insufficient patients (PI). One single determination of fecal chymotrypsin activity and of fecal elastase-1 concentration was realized on each stool. RESULTS: The same relatively important intraindividual variability of fecal proteases was observed in group A and B (mean coefficients of variation (CVs) 36% vs. 40.2% for chymotrypsin, 22.2% vs. 26.8% for elastase-1). No significant PS or severe PI diagnostic discordance was observed between 1, 2, or 3 days of stool collections. CONCLUSION: Our study clearly shows that the determination of fecal proteases on one single stool collected at random is sufficient to evaluate pancreatic exocrine status for PS and severe PI.     

Exocrine Pancreatic Insufficiency

Exocrine pancreatic secretion is controlled by neural and hormonal mechanisms. Pancreatic insufficiency can be caused (1) by diseases that interrupt this integrated process or destroy enzymes in the small intestine and (2) by primary pancreatic disease. Primary and secondary pancreatic insufficiency can be differentiated by comparing the results of reflex and direct stimulatory tests of pancreatic function.     

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201–995 in acromegalic patients

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.     

Abnormalities of circulating immunoreactive pancreatic anionic trypsinogen in cystic fibrosis: an assay artifact due to cross-reacting serum antibodies

In patients with CF, serum pancreatic cationic trypsinogen has proven to be useful for newborn diagnostic screening and also as a test of pancreatic function in the older patient. However, an assay for serum anionic trypsinogen is of no value as a test of pancreatic function in CF due to an apparent artifactual elevation of this enzyme in some patients. In this study, we evaluated the extent of the abnormality in the anionic trypsinogen assay and also elucidated the nature of the interfering material. CF patients were grouped according to the presence (pancreatic insufficiency) or absence (pancreatic sufficiency) of steatorrhea. In CF infants, both serum cationic and anionic trypsinogen levels were greatly elevated. Serum cationic trypsinogen declined with age in patients with pancreatic insufficiency, reaching low or undetectable levels after 6 years. In contrast, serum anionic trypsinogen levels remained normal or elevated in 33% of those over 6 years of age. There was no age-related change in either cationic or anionic trypsinogen among the CF patients with pancreatic sufficiency, and the majority had normal or elevated levels. Serum samples from selected CF patients were separated into IgG and non-IgG fractions using Staph. Protein A columns. Immunoreactive cationic and anionic trypsinogen were detectable in the non-IgG fractions of sera from CF infants and older patients with pancreatic sufficiency. In older CF patients with undetectable serum cationic and anionic trypsinogen, no immunoreactive material was detectable in either the IgG or non-IgG fractions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatostatinoma syndrome accompanied by overproduction of pancreatic polypeptide

A case of somatostatin and pancreatic polypeptide (PP) producing tumor of the pancreas is presented. A 65-year-old woman was admitted for the evaluation of the tumor in the right upper quadrant of the abdomen. Clinical abnormalities included diabetic glucose intolerance, pancreatic insufficiency and marked dilatation of gallbladder. Marked high concentration of plasma PP and low levels of plasma insulin and glucagon were observed before operation. Plasma insulin concentrations in response to oral glucose tolerance test and arginine infusion were markedly low. A large quantity of somatostatin (4,300 ng/g ww) as well as PP (1,340 ng/g ww) was detected in the tumor, and somatostatin cells and PP cells were determined by immunofluorescence studies. After operation, pancreatic insufficiency and glucose intolerance were improved, and the patient made a favorable progress.